Glutathione transferase

Glutathione Transferase (GST) is a family of enzymes that play a crucial role in detoxification by catalyzing the conjugation of the antioxidant glutathione (GSH) to various endogenous and exogenous electrophilic compounds. This process is essential for the metabolism and excretion of toxic substances, as well as for the protection against oxidative stress. GSTs are found in virtually all living organisms, including bacteria, plants, and animals, highlighting their importance in cellular defense mechanisms.

Function

The primary function of glutathione transferase is to facilitate the detoxification process. By attaching glutathione to lipophilic compounds, GSTs make these molecules more water-soluble, thereby enhancing their excretion from the body. This activity is vital for the metabolism of xenobiotics, which are foreign compounds such as drugs and pollutants. Furthermore, GSTs play a significant role in the protection against oxidative damage by removing reactive oxygen species (ROS) and other free radicals, thus contributing to the maintenance of cellular health and preventing DNA damage.

Structure

Glutathione transferases are dimeric proteins, with each monomer consisting of an active site where the conjugation reaction takes place. The structure of GSTs can vary significantly among different species and even among different isoforms within the same species. This structural diversity allows for a wide range of substrates to be processed, contributing to the versatility of GSTs in detoxification processes.

Isoforms

In humans, the GST family is divided into several classes based on their amino acid sequences and structural properties. These include Alpha (α), Mu (μ), Pi (π), Sigma (σ), Theta (θ), and Zeta (ζ) classes, among others. Each class comprises multiple isoforms that are encoded by different genes. The diversity among GST isoforms is a key factor in determining an individual's capacity to detoxify various compounds and, consequently, their susceptibility to certain diseases.

Clinical Significance

Alterations in the expression or activity of GSTs have been linked to a variety of diseases, including cancer, neurodegenerative diseases, and cardiovascular diseases. For instance, certain polymorphisms in GST genes can influence an individual's risk of developing cancer by affecting the detoxification of carcinogens. Additionally, the overexpression of GSTs in tumor cells may contribute to drug resistance by enhancing the detoxification of chemotherapeutic agents.

Environmental Impact

The role of GSTs extends beyond human health, as these enzymes also influence the response of plants and microorganisms to environmental stressors. In plants, GSTs are involved in the detoxification of herbicides and the protection against oxidative damage caused by abiotic stress, such as drought and high salinity. In microorganisms, GSTs contribute to the degradation of pollutants, thereby playing a role in bioremediation processes.

Glutathione transferase Resources
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